B lymphocytes, the central component of the humoral immune response, arise from pluripotent stem cells and progress through a series of differentiation stages before final maturation into antibody-secreting plasma cells. Numerous genes are turned on and off during this progression with some of these genes being B lineage-restricted. Expression of these B cell-specific genes during differentiation ultimately determines the functional program of the B cells as B cells are activated and regulated through their cell-surface molecules. A human B lymphocyte-restricted differentiation antigen CD20 is expressed early during pre-B cell development and persists until plasma cell differentation (Nadler et al., J. Clin. Invest. 74:332 (1984)). Antibody binding to CD20, a phosphoprotein, generates a transmembrane signal which is involved in regulating B cell proliferation and differentiation. The antibody binding results in a rapid increase in phosphorylation of the CD20 molecule without an increase in intracellular Ca.sup.2+ concentration and is believed to mediate inhibition by blocking a required step of the normal activiation process (Tedder et al., Eur. J. of Immunol. 16:881-887 (1986)).
Another kind of transmembrane signaling involves the generation of increased levels of intracellular Ca.sup.2+ (MacDougall et al., Cell 54:229 (1988)). Ion channels in lymphocyte plasma membranes have been directly linked with activation and cell cycle progression (Fukushioma et al., Proc. Natl. Acad. Sci. USA 80:2240-2242 (1983)), and both Ca.sup.2+ channel blocking drugs (e.g., diltiazem) and the absence of extracellular Ca.sup.2+ prevent B cell activation (Dugas et al., Eur. J. Immunol. 16:162-167 (1986)).